title: Tonic activity of Galpha-gustducin regulates taste cell responsivity.
abstract: The taste-selective G protein, alpha-gustducin (alpha-gus) is homologous to alpha-transducin and activates phosphodiesterase (PDE) in vitro. alpha-Gus-knockout mice are compromized to bitter, sweet and umami taste stimuli, suggesting a central role in taste transduction. Here, we suggest a different role for Galpha-gus. In taste buds of alpha-gus-knockout mice, basal (unstimulated) cAMP levels are high compared to those of wild-type mice. Further, H-89, a cAMP-dependent protein kinase inhibitor, dramatically unmasks responses to the bitter tastant denatonium in gus-lineage cells of knockout mice. We propose that an important role of alpha-gus is to maintain cAMP levels tonically low to ensure adequate Ca2+ signaling.
authors.affiliation: Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, United States.
authors.forename: Tod R
authors.initials: TR
authors.lastname: Clapp
authors.forename: Kristina R
authors.initials: KR
authors.lastname: Trubey
authors.forename: Aurelie
authors.initials: A
authors.lastname: Vandenbeuch
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Stone
authors.forename: Robert F
authors.initials: RF
authors.lastname: Margolskee
authors.forename: Nirupa
authors.initials: N
authors.lastname: Chaudhari
authors.forename: Sue C
authors.initials: SC
authors.lastname: Kinnamon
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D000242:Cyclic AMP / Q000378:metabolism*; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013649:Taste; D013650:Taste Buds / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*
chemical_list: D007546:Isoquinolines; D047428:Protein Kinase Inhibitors; D000644:Quaternary Ammonium Compounds; D013449:Sulfonamides; D000242:Cyclic AMP; C524407:GNAT3 protein, mouse; D020962:Heterotrimeric GTP-Binding Proteins; C053525:denatonium saccharide; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide